Generalized giant axonal neuropathy

Peiffer, J.; Schlote, W.; Bischoff, A.; Boltshauser, Eugen; Müller, Günter

doi:10.1007/bf00691956

Cited by 84 publications

(20 citation statements)

References 35 publications

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“…This finding could be the result of one of the following: (1) giant axonal neuropathy (GAN); (2) HMSN type 11; (3) a combination of G A N and HMSN type 11; ( 4 ) a combination of HMSN type I1 and a neurotoxic exposure; and ( 5 ) a new type of HMSN. The feature appears not to represent G A N for the following reasons: (1) this disorder was inherited as an autosomal dominant trait, not as a recessive trait as in G A N 1291; (2) symptomatic onset occurred in the second or later decades and not in infancy; (3) the neuropathy was not associated with kinky hair; (4) the neuropathic involvement was not as generalized or severe as that found in G A N [ l , 3, 16,17,19,20,22); and (5) there was no evidence of central nervous system involvement [3, 13,16,19,20,[22][23][24]291.…”

Section: Cardiovascular Assessmentmentioning

confidence: 98%

Hereditary motor sensory neuropathy type II with neurofilament accumulaion: New finding or new disorder?

Vogel

Gabriel

Goebel

et al. 1985

Annals of Neurology

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Peroneal muscular atrophy is now known to be heterogeneous and to be due to various underlying genetic mechanisms. Exploring this heterogeneity further, we report on a German kinship with the clinical, genetic, and nerve conduction features of hereditary motor and sensory neuropathy type II (HMSN type II) but whose sural nerves on biopsy were found to show infrequent axonal swellings with neurofilament accumulations not previously described. The dominant inheritance and absence of kinky hair set this disorder apart from giant axonal neuropathy. There was no history of toxic exposure to industrial chemicals. We conclude that the disorder either is a new type of HMSN or is HMSN type II with previously unencountered neurofilament accumulations. Neurofilament accumulation indicates that the axon could be a site for primary derangement and may implicate an abnormality of slow axonal flow. In addition, some of the patients exhibited features suggestive of a cardiomyopathy.

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Section: Cardiovascular Assessmentmentioning

confidence: 98%

Hereditary motor sensory neuropathy type II with neurofilament accumulaion: New finding or new disorder?

Vogel

Gabriel

Goebel

et al. 1985

Annals of Neurology

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“…Currently, three forms of inherited giant axonal neuropathy are known: autosomal recessive (45) and autosomal dominant (46) with onset during infancy or childhood and a recently reported congenital form (47). In the recessive form, IF have been shown to be disorganized not only in axons but also in fibroblasts (48), astrocytes, and endothelial and Schwann cells (49). Patients with giant axonal neuropathy also have kinky hair (45).…”

Section: A3mentioning

confidence: 99%

Giant axonal neuropathy: acceleration of neurofilament transport in optic axons.

Monaco¹,

Autilio-Gambetti²,

Zabel³

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

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Giant axonal neuropathies are a group of acquired and inherited human diseases morphologically characterized by accumulation of neurofilaments (NF) in enlargements of preterminal regions of central and peripheral axons. Slow axonal transport was studied in the optic systems of rats treated with 2,5-hexanedione, a toxic compound that produces an experimental model of giant axonal neuropathy. The transport rate of NF and of two other polypeptides of Mr 64,000 and 62,000 were selectively increased. Other components of the slow axonal transport were not affected. Acceleration of labeled NF was also observed when 2,5-hexanedione was given after [35S~methionine administration. Morphometric analysis revealed that the number of NF and the axon size were decreased in regions of optic axons proximal to the enlargements. It is suggested that acceleration of NF transport leads to a longitudinal redistribution of NF: NF decrease proximally and increase distally, forming NF-containing enlargements. Evidence was obtained that polypeptides of Mr 64,000 and 62,000 are cytoskeletal components related to intermediate filaments, normally migrating with the component a of the slow axonal transport. The 2,5-hexanedione axon may provide insight into the pathogenesis of inherited and acquired giant axonal neuropathies and offers a model to investigate the relationship between number of NF and axonal size in central axons.Axonal transport involves the migration of highly ordered complexes of proteins at five distinct rates (1). In mammalian optic axons two groups of proteins, slow component a (SCa) and slow component b (SCb), have transport rates of 0.3 mm/day and 2-3 mm/day, respectively (2). SCa comprises neurofilaments (NF), tubulin, and microtubule-associated proteins, whereas SCb carries over 200 polypeptides, including actin, calmodulin, neuronal-specific enolase, and creatine kinase (3).The use of experimental models has added new insight to the role that disturbances of the axonal transport play in the pathophysiology of human diseases of the central and peripheral nervous systems.Giant axonal neuropathies are a group of diseases comprising toxic as well as inherited conditions (4, 5). The pathological hallmark of these diseases is the presence of masses of NF producing focal enlargements in the preterminal regions of axons. In advanced stages of the neuropathy, the enlargements extend proximally and the distal part of the involved axons eventually undergoes degeneration in several central and peripheral axonal pathways. However, in experimental models no degeneration has been observed in the primary optic pathway despite the presence of numerous enlarged axons (6-8).Methyl n-butyl ketone, n-hexane, and their metabolite 2,5-hexanedione (2,5-HxD) (9, 10) are toxic agents that cause distal giant axonopathies. Methyl n-butyl ketone and n-hexane are widely used as solvents and have caused outbreaks of polyneuropathies among industrial workers (11, 12) and in individuals intentionally inhaling glue vapors (13). The distal gi...

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“…Abnormally accumulated NFs are a pathological hallmark of many human neurodegenerative disorders, including amyotrophic lateral sclerosis [121], Alzheimer's disease [122, 123], Parkinson's disease [124, 125], Charcot-Marie-Tooth [126], giant axonal neuropathy [127], neuronal intermediate filament inclusion disease [128, 129], and diabetic neuropathy [130, 131]. Multiple factors can potentially induce the accumulation of NF, including dysregulation of NF gene expression, NF mutations, defective axonal transport, abnormal posttranslational modifications, and proteolysis [132].…”

Section: Physiology and Pathophysiology Of The Cytoskeletonmentioning

confidence: 99%

Signaling Mechanisms and Disrupted Cytoskeleton in the Diphenyl Ditelluride Neurotoxicity

Pessoa-Pureur

Heimfarth

Rocha

2014

Oxidative Medicine and Cellular Longevity

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Evidence from our group supports that diphenyl ditelluride (PhTe)2 neurotoxicity depends on modulation of signaling pathways initiated at the plasma membrane. The (PhTe)2-evoked signal is transduced downstream of voltage-dependent Ca2+ channels (VDCC), N-methyl-D-aspartate receptors (NMDA), or metabotropic glutamate receptors activation via different kinase pathways (protein kinase A, phospholipase C/protein kinase C, mitogen-activated protein kinases (MAPKs), and Akt signaling pathway). Among the most relevant cues of misregulated signaling mechanisms evoked by (PhTe)2 is the cytoskeleton of neural cells. The in vivo and in vitro exposure to (PhTe)2 induce hyperphosphorylation/hypophosphorylation of neuronal and glial intermediate filament (IF) proteins (neurofilaments and glial fibrillary acidic protein, resp.) in different brain structures of young rats. Phosphorylation of IFs at specific sites modulates their association/disassociation and interferes with important physiological roles, such as axonal transport. Disrupted cytoskeleton is a crucial marker of neurodegeneration and is associated with reactive astrogliosis and apoptotic cell death. This review focuses the current knowledge and important results on the mechanisms of (PhTe)2 neurotoxicity with special emphasis on the cytoskeletal proteins and their differential regulation by kinases/phosphatases and Ca2+-mediated mechanisms in developmental rat brain. We propose that the disrupted cytoskeletal homeostasis could support brain damage provoked by this neurotoxicant.

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Generalized giant axonal neuropathy

Cited by 84 publications

References 35 publications

Hereditary motor sensory neuropathy type II with neurofilament accumulaion: New finding or new disorder?

Hereditary motor sensory neuropathy type II with neurofilament accumulaion: New finding or new disorder?

Giant axonal neuropathy: acceleration of neurofilament transport in optic axons.

Signaling Mechanisms and Disrupted Cytoskeleton in the Diphenyl Ditelluride Neurotoxicity

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